Elevated High-sensitivity C-reactive Protein Research Articles

Parents' use of extreme physical violence is associated with elevated high-sensitivity C-reactive protein in children

BackgroundChildren who grow in settings where parenting is harsh tend to develop a response tendency that may give rise to a chronic pro-inflammatory state. Thus, we aimed to identify if experiencing abuse triggers an increase in the child high sensitivity C-reactive protein (hs-CRP) in a population birth cohort, Generation XXI. MethodsAt cohort participants age of 7 years, information on parents’ disciplinary practices was collected by trained interviewers using the Conflict Tactics Scale Parent-Child version. Venous blood samples were obtained after overnight fast and hs-CRP was quantified. ResultsOf 4175 participants, 44.0% of children reported low frequency of physical violence, 50.1% reported frequent but not severe physical violence, 5.3% reported frequent and severe physical violence, and 0.6% children reported parental extreme physical violence. Higher levels of hs-CRP were observed among children who reported the highest grade of violence severity (58.3%). After adjustment for child's sex, age and parental education, the increasing grade of violence severity increased the odds of higher hs-CRP levels. LimitationsNo significant increase in the levels of hs-CRP was found in children exposed to less severe violence. However that does not mean that those forms of violence have no impact on health in the long-term period. Also, the cross-sectional nature of the study prevents us from concluding the directionality of the effects, although we provided theoretical arguments for the proposed pathway. ConclusionsChildren physically abused by their parent(s) present heightened inflammation levels. Thus, our results show that stressful events may impact inflammatory processes even at very early ages.

Association of neutrophil-to-lymphocyte ratio with non-calcified coronary artery burden in psoriasis: Findings from an observational cohort study

BackgroundInflammation in the form of elevated high-sensitivity c-reactive protein (hs-CRP) has been shown to be critical in the development of atherothrombosis. Psoriasis, a chronic inflammatory skin disease, is associated with high systemic-inflammation, elevated neutrophil-to-lymphocyte ratio (NLR) and accelerated non-calcified coronary artery burden (NCB) by coronary computed tomography angiography (CCTA). We hypothesized that NLR would associate with early, rupture-prone atherosclerosis assessed as NCB independent of hs-CRP. Methods316 consecutive psoriasis participants were recruited with 233 having one-year follow-up as part of a prospective, observational cohort study design. CCTA scans were performed to assess NCB in all three major epicardial coronary arteries. ResultsPatients with above average NLR (>mean: 2.29 ​± ​1.21) were older (mean ​± ​SD; 52.0 ​± ​12.8 vs. 47.9 ​± ​12.6, p ​= ​0.002), had higher hs-CRP (med. IQR: 2.3 (0.9–7.3) vs. 1.4 (0.7–3.2), p ​= ​0.001) and had higher NCB (mean ​± ​SD; 1.21 ​± ​0.58 vs. 1.13 ​± ​0.49, p ​= ​0.018) when compared to patients with below average NLR. NLR associated with psoriasis area severity index score (β ​= ​0.14, p ​= ​0.017), hs-CRP (β ​= ​0.16, p ​= ​0.005), as well as NCB independent of traditional risk factors, body mass index, statin use and hs-CRP (β ​= ​0.08, p ​= ​0.009). One year of biologic therapy for psoriasis was associated with a reduction in NLR (−14.5%, p ​< ​0.001), and this change in NLR associated with change in NCB in fully adjusted models and beyond hs-CRP (β ​= ​0.17, p ​= ​0.002). ConclusionNLR associated with psoriasis severity, hs-CRP and NCB at baseline. Biologic therapy reduced NLR over time and this change in NLR associated with the change in NCB at one-year. Taken together, these findings suggest that NLR may capture psoriasis patients at higher risk of NCB due to residual inflammation not fully captured by hs-CRP.

Association between Dietary Macronutrient Intake and High-Sensitivity C-Reactive Protein Levels among Obese Women in Kuantan, Malaysia

Elevated high-sensitivity C-reactive protein (hs-CRP) levels may be associated with an increased risk of cardiovascular disease (CVD). In general, an individual’s dietary intake may influence the hs-CRP level. However, evidence on the influence of dietary macronutrient intake on hs-CRP levels among obese Malaysian women remains fragmented. Therefore, this study aims to investigate the association between the hs-CRP level and dietary macronutrient intake of obese adults living in Kuantan. The assessment of 24-hour dietary recall and venous hs-CRP levels were investigated in 67 women with a body mass index of 27.5 to 39.9 kg/m². The findings revealed that obese women living in Kuantan had elevated hs-CRP levels (median = 7.95 mg/L, IQR = 7.90) and a significant negative correlation between the hs-CRP level and total dietary fiber intake (r = 0.205, p =.014). In conclusion, this study suggests that certain macronutrients, particularly dietary fiber, seem to be associated with elevated hs-CRP in obese women. Hence, this information could help assess and manage low-grade chronic inflammation and underlying obesity-related conditions.

Study of high-sensitivity C-Reactive protein levels in subjects with type 2 diabetes mellitus

Introduction: The Diabetes mellitus was characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, and protein metabolism resulting from defects in insulin secretion, insulin action, or both. The two broad categories of diabetes are type 1 and type 2. Type 2 Diabetes Mellitus (T2DM) is the most common form of diabetes. The role of elevated high sensitivity C-reactive protein (hs-CRP) as a risk marker for cardiovascular diseases, including coronary heart disease, stroke and peripheral arterial disease is well established through consistent results from a number of prospective studies. More recent data suggest that hs-CRP is superior to other markers of inflammation for risk evaluation. Materials and Methods: The present study was conducted over a period of one year on outpatients attending the General Medicine Department at Narayana General Hospital, Nellore. The study was undertaken on 50 type 2 Diabetes mellitus and 50 normal healthy controls. Both male and females in the age group of 35 – 70 years were included. Results: Fasting blood glucose, post prandial blood glucose, and hs-CRP levels was measured in 50 T2DM cases and 50 age matched healthy controls. The mean and standard deviation were calculated for all the Biochemical parameters. The significance between the groups were determined using Student t- test for Equality of means. The p-value of < 0.05 was considered significant. Conclusion: This study concludes that there is increase in hs-CRP levels in T2DM cases compared with controls. hs-CRP is an inflammatory marker and has role in atherosclerosis. From this study it is observed that there is moderate correlation between hs-CRP levels and it increases the risk of atherosclerosis. Keywords: Diabetes Mellitus, hs-CRP, Hyperglycemia, Inflammation.

Prognostic Impact of High-Sensitivity C-Reactive Protein in Patients Undergoing Percutaneous Coronary Intervention According to BMI.

The aim of this study was to determine the prevalence and prognostic implications of elevated high-sensitivity C-reactive protein (hsCRP) in patients undergoing percutaneous coronary intervention (PCI) according to body mass index (BMI). Whereas elevated hsCRP predicts adverse clinical outcome after PCI in the general population, the impact of BMI on its prognostic utility remains unclear. Data from 14,140 patients who underwent PCI between January 2009 and June 2017 at a large tertiary care center were analyzed. Patients were divided into 4 BMI categories: normal (BMI 18.5 to<25kg/m2, n=2,808), overweight (BMI 25 to<30kg/m2, n=6,015), obese (BMI 30 to<35kg/m2, n=3,490), and severely obese (BMI≥35kg/m2, n=1,827). Elevated hsCRP was defined as >3mg/l. The primary endpoint of interest was the occurrence of major adverse cardiac events (MACE; defined as death, myocardial infarction, or target vessel revascularization) within 1 year after PCI. Elevated hsCRP was present in 18.9%, 23.6%, 33.3%, and 47.7% of the normal, overweight, obese, and severely obese groups, respectively. MACE rates were consistently higher in patients with elevated hsCRP across all BMI categories (normal, 13.4% vs. 8.3%; overweight, 11.2% vs. 7.2%; obese, 10.6% vs. 7.5%; severely obese, 11.9% vs. 6.5%; p<0.01 for all). After multivariate adjustment, hsCRP elevation remained significantly associated with MACE independent of BMI (hazard ratios: normal, 1.43 [95% confidence interval: 1.04 to 1.95]; overweight, 1.56 [95% confidence interval: 1.21 to 1.88]; obese, 1.40 [95% confidence interval: 1.06 to 1.84]; severely obese, 1.92 [95% confidence interval: 1.35 to 2.75]; p<0.05 for all). Among patients undergoing PCI, the prevalence of hsCRP elevation progressively increased with higher BMI. Measurement of hsCRP facilitates prognostic risk assessment for adverse outcome after PCI across a broad range of BMI.

The Finnish Diabetes Risk Score (FINDRISC), incident diabetes and low-grade inflammation

AimsThe FINDRISC was created to predict the development of type 2 diabetes mellitus (T2DM). Since T2DM associates with inflammation we evaluated if the FINDRISC could predict either current or incident T2DM, and elevated high sensitivity C-reactive protein (hs-CRP). Methods41,880 people (age 41.9 ± 9.7 years; 31% female) evaluated between 2008 and 2016 were included. First, the cross-sectional association between the FINDRISC with presence of either T2DM or hs-CRP ≥ 2.0 mg/L was tested. After a 5 ± 3 years follow-up we tested the score predictive value for incident T2DM and inflammation in respectively 10,559 individuals without diabetes and in a subset of 2,816 individuals having no elevated hs-CRP at baseline. ResultsIn the cross sectional analysis the FINDRISC was associated with both T2DM (OR 1.24, 95% CI: 1.23–1.26, P < 0.001) and inflammation (OR 1.10, 95% CI: 1.09–1.11, P < 0.001) per FINDRISC unit, as well as in longitudinal analyses (OR 1.17, 95% CI: 1.14–1.20, P < 0.001; and OR 1.04, 95% CI: 1.02–1.07, P < 0.001; respectively, per FINDRISC unit). The C-statistic for incident T2DM and inflammation was 0.79 (95% CI 0.77–0.82) and 0.55 (95% CI 0.53–0.58), respectively. ConclusionThe FINDRISC shows good discrimination for incident T2DM but less for inflammation.

Abstract 14093: High-Sensitivity C-reactive Protein Modifies the Effect of Lipoprotein (a) on Cardiovascular Risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Lipoprotein (a) (Lp(a)) and inflammation, as represented by elevated high-sensitivity C-reactive protein (hsCRP) concentration, are both considered as risk-enhancers in the 2018 AHA/ACC Cholesterol guidelines. However, little is known as to whether the association of Lp(a) with atherosclerotic cardiovascular disease (ASCVD) risk is modified by inflammation. Objective: We assessed whether hsCRP modifies the association of Lp(a) with ASCVD risk. Methods: MESA participants with baseline hsCRP and Lp(a) levels were included. Incident ASCVD events were ascertained from baseline through 2017. Time to incident ASCVD was analyzed using Kaplan Meir curves. Cox proportional hazards models were used to assess the association between Lp(a), hsCRP, and time to ASCVD events adjusting for covariates. Results: The study included 4,654 participants with mean age of 62 and 52.5% females (1,702 Caucasians, 557 Chinese Americans, 1,336 African Americans and 1,059 Hispanics). With a mean 13.6-year follow-up, 676 ASCVD events occurred among 4,609 participants (Figure 1). In participants with hsCRP &lt;2mg/L, the association of Lp(a) (per 1 Log unit increase) and risk for ASCVD as represented by hazard ratio (HR) and 95%CI was 1.01 (0.79, 1.28). In subjects with hsCRP ≥2mg/L, the risk increased to 1.26 (1.01, 1.58). When compared to the reference group with Lp(a) &lt;50mg/dL and hsCRP &lt;2mg/L, the risk for ASCVD in participants with Lp(a) ≥50mg/dL and hsCRP &lt;2mg/L was 1.13 (0.85, 1.50) and in those with Lp(a) &lt;50mg/dL and hsCRP ≥2mg/L was 1.09 (0.92, 1.31). The risk increased significantly to 1.62 (1.26, 2.07) in participants with Lp(a) ≥50mg/dL and hsCRP ≥2mg/L. Conclusions: Lp(a)-related ASCVD risk is modified by hsCRP levels. The findings of this analysis suggest that Lp(a) may serve as a risk enhancing factor in individuals with hsCRP level ≥2mg/L. Future studies are needed to determine whether Lp(a) is associated with risk of ASCVD in the absence of subclinical inflammation.

Prognostic Value of Soluble Urokinase-Type Plasminogen Activator Receptor and High-Sensitivity C-Reactive Protein on Postoperative Mortality in Patients Undergoing Elective On-Pump Cardiac Surgery

Elevated soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP) have been associated with increased mortality in patients with cardiovascular disease. The aim of the present study was to explore the relationship between suPAR and hsCRP values and associated mortality after elective cardiac surgery. A secondary aim was to assess whether a combined risk model of European System for Cardiac Operative Risk Evaluation (EuroSCORE II), suPAR, and/or hsCRP would improve the prognostic accuracy compared with EuroSCORE II alone. Retrospective observational study. Single-center, university hospital. Adult patients admitted for elective on-pump cardiac surgery were included. Biobank blood samples were obtained from previous research projects at a tertiary heart center from 2012 to 2018. None. A total of 931 patients were included. Kaplan-Meier and Cox proportional hazard analyses were used to explore a potential association between preoperative suPAR and hsCRP values and all-cause mortality up to one year after surgery. Thirty-day mortality was predicted from suPAR, hsCRP, and EuroSCORE II by logistic regression and compared using area under the receiver operating characteristics curve and Brier scores. After adjustment for known confounders, a doubling of suPAR and hsCRP corresponded to a hazard ratio for all-cause mortality of 2.27 (95% confidence interval 1.65-3.11; p < 0.001) and 1.26 (95% confidence interval 1.07-1.49; p = 0.005), respectively. However, adding the biomarkers to EuroSCORE II did not improve prediction/discrimination with respect to 30-day mortality. Elevated preoperative levels of suPAR and hsCRP were associated with all-cause mortality in elective cardiac surgery patients. However, inclusion of biomarkers did not improve the prognostic accuracy of EuroSCORE II.

Interleukin-1Beta and risk of premature death and MACE in patients with myocardial infarction

Abstract Background Inhibition of the interleukin-1β (IL-1β) innate immunity pathway is associated with anti-inflammatory effects and a reduced risk of recurrent cardiovascular events in stable patients with previous myocardial infarction (MI) and elevated high sensitivity C-reactive protein (hs-CRP). However, the prognosis value of IL-1β level in acute myocardial infarction patients has never been evaluated. We aim to assess the association between IL-1β level with all-cause mortality in patients with acute ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention and the interplay between IL-1β and hs-CRP concentrations on the risk of premature death. Methods IL-1β concentration was measured among 1398 STEMI patients enrolled in a prospective cohort study. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90-days and one-year using a multivariate-cox proportional regression analysis. Major cardiovascular events (MACE) were also analyzed. Results In a STEMI population, IL-1β concentration measured at admission was independently associated with all-cause mortality at 90 days (adjusted hazard ratio [adjHR], 1.43 per 1SD increase; 95% CI, 1.12 to 1.83; p&amp;lt;0.005). The relation was nonlinear, and we identified a threshold of IL-1β &amp;gt;10 pg/mL that was markedly associated with higher mortality rates at 90 days (adjHR: 2.80; 95% CI: 1.63–4.80, p=0.0002) and one-year (adjHR: 1.75; 95% CI: 1.09–2.78, p=0.019), regardless of the hs-CRP concentration. The relationship was even stronger when considering cardiovascular mortality and MACE at 90 days (adjHR: 2.31; 95% CI: 1.30–4.10, p=0.004 and 2.17; 95% CI: 1.24–3.80, p=0.006) and at one year (adjHR: 2.26; 95% CI: 1.31–3.87, p=0.03 and 2.25; 95% CI: 1.33–3.79, p=0.004). Conclusion IL-1β measured at admission in acute MI patients is associated with the risk of mortality and recurrent major cardiovascular events, regardless of the CRP level. A threshold of 10 pg/mL identifies patients at higher risk of events. Survival Funding Acknowledgement Type of funding source: None

Synergistic Effects and Sex Differences in Anthropometric Measures of Obesity and Elevated High-Sensitivity C-Reactive Protein Levels.

Background: It remains unclear which anthropometric measure best predicts elevated high-sensitivity C-reactive protein (hs-CRP) levels. This study investigated the association and synergistic interaction of two obesity indices with elevated hs-CRP levels in a national sample of Korean adults, stratified by sex. Methods: The present cross-sectional study used data from the 2015–2018 Korea National Health and Nutrition Examination Survey of 18,610 subjects aged ≥20 years after excluding those with missing variables. Multiple logistic regression analyses and chi-squared tests were performed to investigate the association between body mass index (BMI) and waist circumference (WC) with elevated hs-CRP levels. Interaction analysis was used to examine the synergistic effect between BMI and WC on the risk of having elevated hs-CRP levels. Results: Elevated hs-CRP levels exceeding 3 mg/L were present in 9.3% and 7.5% of men and women, respectively. The relationship between each obesity index and elevated hs-CRP levels was significant in women (high WC (odds ratio [OR] = 1.77, 95% confidence interval [CI] = 1.24–2.54), high BMI (OR = 2.08, 95% CI = 1.58–2.74)) but not in men (high WC (OR = 1.19, 95% CI = 0.86–1.64), high BMI (OR = 0.99, 95% CI = 0.77–1.29)). Furthermore, combined measures of the two obesity indices and interaction analysis results revealed a synergistic association in men (OR = 1.57, 95% CI = 1.33–1.85; relative excess risk due to interaction (RERI) = 0.39, 95% CI = −0.09–0.86), and women (OR = 3.70, 95% CI = 3.09–4.43; RERI = 0.85, 95% CI = −0.06–1.75). Conclusion: BMI and WC were significantly associated with a risk of elevated hs-CRP levels in women but not in men. Nevertheless, significant synergistic interactions were seen in combined measures of BMI and WC, regardless of sex. These findings emphasize the need to use both measures of adiposity concurrently in the assessment of obesity and when identifying cardiovascular risk.

Prevalence of Physical Frailty and Its Multidimensional Risk Factors in Korean Community-Dwelling Older Adults: Findings from Korean Frailty and Aging Cohort Study.

Frailty is defined as a state of increased vulnerability to stressors, and it predicts disability and mortality in the older population. This study aimed to investigate the standardized prevalence and multidimensional risk factors associated with frailty among Korean community-dwelling older adults. We analyzed the baseline data of 2907 adults aged 70–84 years (mean age 75.8 ± 3.9 years, 57.8% women) in the Korean Frailty and Aging Cohort Study. The Fried frailty phenotype was used to define frailty. Analyzed data included sociodemographic, physical, physical function, biological, lifestyle, health condition, medical condition, psychological, and social domains. Data were standardized using the national standard population composition ratio based on the Korean Population and Housing Census. The standardized prevalence of frailty and prefrailty was 7.9% (95% confidence interval (CI) 6.8–8.9%) and 47.0% (95% CI, 45.1–48.8%), respectively. The following 14 risk factors were significantly associated with frailty: at risk of malnutrition, sarcopenia, severe mobility limitation, poor social capital, rural dwellers, depressive symptoms, poor self-perceived health, polypharmacy, elevated high-sensitivity C-reactive protein, elevated glycosylated hemoglobin, low 25-hydroxy vitamin D level, longer Timed Up and Go, and low Short Physical Performance Battery score (p < 0.05). Physiconutritional, psychological, sociodemographic, and medical factors are strongly associated with frailty.

Clinical characteristics and survival analysis in critical and non-critical patients with COVID-19 in Wuhan, China: a single-center retrospective case control study

Since the outbreak of COVID-19 in China at the end of 2019, the world has experienced a large-scale epidemic caused by the SARS-CoV-2. The epidemiological and clinical course of COVID-19 patients has been reported, but there have been few analyses about the characteristics, predictive risk factors, and outcomes of critical patients. In this single-center retrospective case–control study, 90 adult inpatients hospitalized at Tongji Hospital (Wuhan, China) were included. Demographic, clinical, laboratory tests, and treatment data were obtained and compared between critical and non-critical patients. We found that compared with non-critical patients, the critical patients had higher SOFA score and qSOFA scores. Critical patients had lower lymphocyte and platelet count, elevated D-dimer, decreased fibrinogen, and elevated high-sensitivity C-reactive protein (hsCRP), and interleukin-6(IL-6). More critical patients received treatment including antibiotics, anticoagulation, corticosteroid, and oxygen therapy than non-critical ones. Multivariable regression showed higher qSOFA score and elevation of IL-6 were related to critical patients. Antibiotic usage and anticoagulation were associated with decreased in-hospital mortality. And critical grouping contributed greatly to in-hospital death. Critical COVID-19 patients have a more severe clinical course. qSOFA score and elevation of IL-6 are risk factors for critical condition. Non-critical grouping, positive antibiotic application, and anticoagulation may be beneficial for patient survival.

COVID-19 recovery: potential treatments for post-intensive care syndrome

COVID-19 recovery: potential treatments for post-intensive care syndrome

Novel serological biomarkers for inflammation in predicting disease severity in patients with COVID-19

BackgroundPatients with severe coronavirus disease 2019 (COVID-19) develop acute respiratory distress and multi-system organ failure and are associated with poor prognosis and high mortality. Thus, there is an urgent need to identify early diagnostic and prognostic biomarkers to determine the risk of developing serious illness. MethodsWe retrospectively analyzed 114 patients with COVID-19 at the Jinyintan Hospital, Wuhan based on their clinical and laboratory data. Patients were categorized into severe and mild to moderate disease groups. We analyzed the potential of serological inflammation indicators in predicting the severity of COVID-19 in patients using univariate and multivariate logistic regression, receiver operating characteristic curves, and nomogram analysis. The Spearman method was used to understand the correlation between the serological biomarkers and duration of hospital stay. ResultsPatients with severe disease had reduced neutrophils and lymphocytes; severe coagulation dysfunction; altered content of biochemical factors (such as urea, lactate dehydrogenase); elevated high sensitivity C-reactive protein levels, neutrophil–lymphocyte, platelet-lymphocyte, and derived neutrophil–lymphocyte ratios, high sensitivity C-reactive protein-prealbumin ratio (HsCPAR), systemic immune-inflammation index, and high sensitivity C-reactive protein-albumin ratio (HsCAR); and low lymphocyte-monocyte ratio, prognostic nutritional index (PNI), and albumin-to-fibrinogen ratio. PNI, HsCAR, and HsCPAR correlated with the risk of severe disease. The nomogram combining the three parameters showed good discrimination with a C-index of 0.873 and reliable calibration. Moreover, HsCAR and HsCPAR correlated with duration of hospital stay. ConclusionTaken together, PNI, HsCAR, and HsCPAR may serve as accurate biomarkers for the prediction of disease severity in patients with COVID-19 upon admission/hospitalization.

Pulmonary tuberculosis masquerading as coronavirus disease 2019 in an HIV-infected individual with advanced immune suppression

Pulmonary tuberculosis masquerading as coronavirus disease 2019 in an HIV-infected individual with advanced immune suppression

Association Between Long-term Functional Outcome and Change in hs-CRP Level in Patients With Acute Ischemic Stroke.

Elevated high-sensitivity C-reactive protein (hs-CRP) has been suggested as a risk factor for ischemic stroke. However, the predictive value of hs-CRP for long-term outcomes is poorly defined. Therefore, we conducted this study to evaluate whether change in hs-CRP level plays a role in the prognostic value of long-term functional disability. We studied 263 patients with acute ischemic stroke and 104 healthy controls (67.5±11.26 and 68.17±11.21 y, respectively). hs-CRP was measured on admission and on the seventh day of hospitalization. The patients were classified into 2 groups on the basis of difference in hs-CRP level from admission to the seventh day of hospitalization (group 1, hs-CRP on admission>the seventh hospital day; group 2, hs-CRP on admission<the seventh hospital day). The correlation between change in hs-CRP level and functional disability using the modified Rankin Scale score (mRS) at 1, 3, 6, and 12 months after stroke onset was analyzed. We observed significant differences between initial hs-CRP level in all patients (0.96±2.82 mg/dL) and healthy controls (0.34±0.71 mg/dL, P=0.029). Significant differences in mRS at the 4 different timepoints was not observed between 2 groups (P=0.453, 0.225, 0.229, and 0.396, respectively). The Spearman rank-order correlation coefficients showed that change in hs-CRP level increasingly differed over time and was statistically correlated with mRS (coefficient/P: at 1 mo, 0.139/0.024; at 3 mo, 0.149/0.015; at 6 mo, 0.147/<0.001; and at 12 mo, 0.134/0.03). However, the results were very low correlation coefficients, despite their statistical significance. This study did not clearly show an association between increase in hs-CRP level over time and long-term functional disability.

Short-term effect of low-dose colchicine on inflammatory biomarkers, lipids, blood count and renal function in chronic coronary artery disease and elevated high-sensitivity C-reactive protein

AimsInflammation plays a pivotal role in atherothrombosis. Colchicine is an anti-inflammatory drug that may attenuate this process. Cardiovascular protective effects of anti-inflammatory drugs, however, seem to be limited to patients with a biochemical response. We therefore investigated whether short-term exposure to colchicine reduced inflammatory markers and whether additional laboratory changes occur in patients with chronic coronary artery disease.Methods & resultsIn 138 consecutive patients with chronic coronary artery disease and a high sensitivity C-reactive Protein (hs-CRP) ≥ 2 mg/L, inflammatory markers, lipids, haematologic parameters and renal function were measured at baseline and after 30 days exposure to colchicine 0.5mg once daily. Hs-CRP decreased from baseline 4.40 mg/L (interquartile range [IQR] 2.83–6.99 mg/L) to 2.33 mg/L (IQR 1.41–4.17, median of the differences -1.66 mg/L, 95% confidence interval [CI] -2.17 – -1.22 mg/L, p-value <0.01), corresponding to a median change from baseline of -40%. Interleukin-6 decreased from 2.51 ng/L (IQR 1.59–4.32 ng/L) to 2.22 ng/L (median of the differences -0.36 ng/L, 95%CI -0.70 – -0.01 ng/L, p-value 0.04), corresponding to a median change from baseline of -16%. No clinically relevant changes in lipid fractions were observed. Both leukocyte and thrombocyte count decreased (median change from baseline -7% and -4% respectively). Estimated glomerular filtration rate decreased with a mean change from baseline of -2%.ConclusionIn patients with chronic coronary artery disease and elevated hs-CRP, one-month exposure to colchicine 0.5 mg once daily was associated with a reduction of inflammatory markers. A small effect was seen on white blood cell count and platelet count, as well as a small decrease in estimated glomerular filtration rate.

Interleukin-1β and Risk of Premature Death in Patients With Myocardial Infarction

BackgroundInhibition of the interleukin (IL)-1β innate immunity pathway is associated with anti-inflammatory effects and a reduced risk of recurrent cardiovascular events in stable patients with previous myocardial infarction (MI) and elevated high-sensitivity C-reactive protein (hs-CRP). ObjectivesThis study assessed the association between IL-1β level with all-cause mortality in patients with acute ST-segment elevation MI who underwent primary percutaneous coronary intervention and the interplay between IL-1β and hs-CRP concentrations on the risk of premature death. MethodsIL-1β concentration was measured in 1,398 patients with ST-segment elevation MI who enrolled in a prospective cohort. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90 days and 1 year using multivariate Cox proportional regression analysis. Major adverse cardiovascular events (MACEs) were analyzed. ResultsIL-1β concentration measured at admission was associated with all-cause mortality at 90 days (adjusted hazard ratio [adjHR]: 1.47 per 1 SD increase; 95% confidence interval [CI]: 1.16 to 1.87; p < 0.002). The relation was nonlinear, and the highest tertile of IL-1β was associated with higher mortality rates at 90 days (adjHR: 2.78; 95% CI: 1.61 to 4.79; p = 0.0002) and at 1 year (adjHR: 1.93; 95% CI: 1.21 to 3.06; p = 0.005), regardless of the hs-CRP concentration. Significant relationships were equally observed when considering cardiovascular mortality and MACEs at 90 days (adjHR: 2.42; 95% CI: 1.36 to 4.28; p = 0.002, and adjHR: 2.29; 95% CI: 1.31 to 4.01; p = 0.004, respectively) and at 1 year (adjHR: 2.32; 95% CI: 1.36 to 3.97; p = 0.002, and adjHR: 2.35; 95% CI: 1.39 to 3.96; p = 0.001, respectively). ConclusionsIL-1β measured at admission in patients with acute MI was independently associated with the risk of mortality and recurrent MACEs.

Abstract CT287: CANOPY-A: A phase III, multicenter, randomized trial evaluating canakinumab versus placebo as adjuvant therapy in patients with completely resected non-small cell lung cancer (NSCLC)

Abstract Background: In the CANTOS study, treatment with canakinumab (selective IL-1β inhibitor) was associated with reduced incidence and mortality of NSCLC in patients with stable post-myocardial infarction who had elevated high-sensitivity C-reactive protein (hs-CRP) levels. The results provided a rationale to investigate the therapeutic role of canakinumab in NSCLC. Methods: The phase III, multicenter, randomized, double-blind, placebo-controlled CANOPY-A study (NCT03447769) is evaluating the efficacy and safety of canakinumab as adjuvant therapy in adult patients with completely resected NSCLC. Patients with AJCC/UICC v.8 stages II-IIIA and IIIB (T&amp;gt;5 cm, N2), any histology, completely resected (R0) NSCLC who have completed adjuvant cisplatin-based chemotherapy (≥2 cycles) and radiation therapy (if applicable) are eligible. Patients must not have had prior neoadjuvant chemotherapy or neoadjuvant radiotherapy. Patients (~1500) are randomized 1:1 to receive canakinumab (200 mg Q3W, SC) or placebo (Q3W, SC) for 18 cycles or until NSCLC disease recurrence as determined by investigator, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or patient, start of a new antineoplastic therapy, death, or loss to follow-up. Randomization is stratified by AJCC/UICC v.8 stage (IIA vs IIB vs IIIA vs IIIB with T&amp;gt;5 cm, N2 disease), tumor histology (squamous vs non-squamous), and region (western Europe and North America vs eastern Asia vs rest of the world). Primary objective is disease-free survival (DFS) per local investigator assessment. Secondary objectives are overall survival (OS), lung cancer specific survival, safety, pharmacokinetics, immunogenicity, and patient reported outcomes. Adult patients with stage IIA-IIIA, IIIB (N2 disease only) NSCLC who are candidates for complete resection surgery (and therefore prospective candidates for the main study) will be asked to participate in a biomarker sub-study to understand how resection surgery may impact biomarkers involved in the IL-1β inflammatory pathway as well as mutations present in blood. For all patients participating into the sub-study, the levels of hs-CRP, other cytokines, and additional biomarkers in blood will be assessed at pre- and post-surgery (endpoint: summary statistics of hs-CRP and other pharmacodynamics [PD] biomarkers). For patients who will also enroll into the main study, possible associations between pre- and post-surgery biomarker levels with canakinumab efficacy will be determined (endpoint: DFS and OS by hs-CRP and other PD biomarkers). The CANOPY-A study is currently enrolling. As of Jan 13, 2020, there are 307 study locations. Citation Format: Edward B. Garon, Andrea Ardizzoni, Fabrice Barlesi, Byoung Chul Cho, Pedro De Marchi, Yasushi Goto, Dariusz Kowalski, Shun Lu, Luis Paz-Ares, David R. Spigel, Alexander Spira, Michael Thomas, Mimi Leung, Jason Baum, Zewen Zhu, Bijoyesh Mookerjee, James Chih-Hsin Yang. CANOPY-A: A phase III, multicenter, randomized trial evaluating canakinumab versus placebo as adjuvant therapy in patients with completely resected non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT287.

Abstract CT286: CANOPY program clinical trials: Canakinumab (Cana) in patients (pts) with non-small cell lung cancer (NSCLC)

Abstract Background: In the CANTOS study, treatment (tx) with Cana (selective IL-1β inhibitor) was associated with reduced incidence and mortality of NSCLC in stable post-myocardial infarction pts with elevated high-sensitivity C-reactive protein levels. The results provided a rationale to investigate the therapeutic role of Cana in NSCLC. Methods: The phase (ph) 2, open-label CANOPY-N study (NCT03968419) is evaluating Cana or pembrolizumab (pembro) alone or in combination as neoadjuvant tx in stage IB-IIIA, tx-naive NSCLC pts eligible for primary resection (except N2 and T4 tumors) with planned surgery in 4-6 weeks (wks) from the 1st dose of study tx. Pts (~110) are randomized 2:2:1 to Cana (2 doses 200 mg SC Q3W), Cana + pembro, or pembro (2 doses 200 mg iv Q3W) for 2 three-wk cycles. Randomization (R) stratification: histology (squamous [sq] vs non-sq). Primary endpoint: major pathological response rate at time of surgery.CANOPY-A (NCT03447769), CANOPY-1 (NCT03631199), and CANOPY-2 (NCT03626545) are ph 3, multicenter, double-blind studies. In CANOPY-A (Cana in adjuvant setting), pts (~1500) with stages IIA-IIIA and IIIB (T&amp;gt;5 cm N2), any histology, completely resected (R0) NSCLC post cisplatin-based chemotherapy (CTx) and radiation therapy (if applicable) are randomized 1:1 to Cana (200 mg SC Q3W)/placebo (PBO; SC Q3W) for 18 cycles. R stratification: AJCC/UICC v.8 stage (IIA vs IIB vs IIIA vs IIIB with T&amp;gt;5 cm, N2 disease), histology (sq vs non-sq), region (western Europe and North America vs eastern Asia vs rest of the world). Primary endpoint: disease-free survival. CANOPY-1 and CANOPY-2 consist of Part 1 (open-label, safety run-in; enrollment complete) and Part 2 (randomized 1:1, PBO-controlled, efficacy &amp; safety; ongoing). CANOPY-1 eligibility: pts with previously untreated stages IIIB/IIIC or IV NSCLC and known PD-L1 status (for Part 2), without EGFR sensitizing mutations and/or ALK rearrangements. Part 1 (3 cohorts of ~9 pts each, based on different platinum-CTx): to confirm the recommended phase 3 regimen (RP3R) for Cana. In Part 2, pts (~600) are randomized to Cana (200 mg SC Q3W)/PBO + pembro + CTx for 4 cycles, followed by maintenance tx (Cana/PBO + pembro ± pemetrexed) until progressive disease (PD). R stratification: PD-L1 status (tumor proportion score &amp;lt;1% vs ≥1%), histology (sq vs non-sq), geographic region (eastern Asia vs North America + western Europe vs rest of the world). Screening has ceased as of Dec 9, 2019. In CANOPY-2, pts with stage IIIB-IV NSCLC, who received prior PD-(L)1 inhibitor therapy and platinum-based CTx, without EGFR sensitizing mutations and/or ALK rearrangements are eligible. Part 1 (~9 pts): to confirm the RP3R of Cana + docetaxel. In Part 2, pts (~226) are randomized to receive Cana (200 mg SC Q3W)/PBO + docetaxel (75 mg/m2 iv Q3W) until PD. R stratification: number of prior lines of therapy in advanced setting (1 vs 2 prior lines of therapy) and histology (sq vs non-sq). Primary endpoints: CANOPY-1 and CANOPY-2 Part 1: to confirm RP3R of the combination; CANOPY-1 Part 2: progression-free survival and overall survival (OS); CANOPY-2 Part 2: OS. Citation Format: Luis Paz-Ares, Edward B. Garon, Tony Mok, Andrea Ardizzoni, Fabrice Barlesi, Byoung Chul Cho, Gilberto de Castro, Pedro De Marchi, Enriqueta Felip, Yasushi Goto, Alastair Greystoke, Shun Lu, Darren Wan-Teck Lim, Martin Reck, Benjamin J. Solomon, David R. Spigel, Daniel SW Tan, Michael Thomas, James Chih-Hsin Yang, Jay M. Lee, Pilar Garrido, Edward Kim, Bruce E. Johnson. CANOPY program clinical trials: Canakinumab (Cana) in patients (pts) with non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT286.